*7.1.2 Modulation of the biofilm architecture to eradicate biofilms*

Biofilm extracellular polymeric substances (EPS) called the matrix is composed of proteins, polysaccharides, and eDNA and loosely links bacteria within the biofilm. They are responsible for irreversible cellular attachment, improve mechanical stability, and maintain secreted enzymes [41]. Theoretically, biofilm EPS matrix targeted agents have the possibility to interfere with the growth of biofilm, their dislocation, destabilization, detachment, sensitization, and increase access of antibiotics [38]. An example is the inhibition of biofilm formation by a variety of Gram-positive and Gram-negative organisms, e.g., *S. epidermidis and P. aeruginosa*. Specifically, deoxyribonuclease I (DNase I) cleaves single-stranded or double-stranded DNA at phosphodiester bonds that make up the phosphate backbone during the addition of DNase I [41–43].

*Bacterial Biofilm Eradication in Human Infections DOI: http://dx.doi.org/10.5772/intechopen.113341*

#### *7.1.3 Electrochemical biofilm eradication*

One of the new perspectives in eradicating biofilms is through electrochemical techniques. The mechanism of action involved is the formation of H2O2, which is a result of the partial reduction of oxygen on metal surfaces [44]. This stimulates an electric current that affects the organization of biological membranes, cellular processes [45], cell behavior [46], bacterial respiratory rate, and oxidation of proteins, likewise cell electrophysiology [47]. The eradication of biofilm using electrochemically generated biocides varies depending on biocide concentration, exposure time, biofilm thickness and/or growth stage, and bacterial strain, as observed [44]. An example of experiment carried out *in vivo* on *Acinetobacter baumannii* grown as biofilms on porcine explants showed it could be overlaid with the same e-scaffold, and this significantly reduced viable bacteria by about 1000 folds [48].

#### **7.2 Strategies for combating bacterial biofilm infections**

Strategies to combat biofilm formation range from the control by surface adhesins to the control by cell-to-cell communication pathways [49]. Three strategies have been identified, which include (a) altering abiotic surface characteristics to prevent biofilm formation; (b) regulating the signaling pathways to inhibit biofilm formation and stimulate biofilm dispersal; and (c) applying external forces to eradicate the biofilm (**Figure 6**) [26].

#### *7.2.1 Altering abiotic surface characteristics to prevent biofilm formation*

Here two strategies are characterized, that is, treating abiotic surfaces and coating surfaces (**Figure 6A**–**B**) [26]. Treatment relies on changing the characteristics of surface material like smoothness and wettability through thermal cycling and UV irradiation or hydrophilicity [50] and coating surfaces with polymers, trimethyl-silane (TMS)/O2, and antimicrobial peptides in order to prevent biofilm attachment [26].

#### *7.2.2 Regulation of signaling pathways to inhibit biofilm*

Examples of pathways inhibition are those based on quorum sensing that triggers a cascade of intracellular signaling events, eventually regulating different physiological phenotypes after binding to their matching receptors [51], inhibiting biofilm-related genes expression through the interfering with the QS signaling pathway [26], and inhibition based on nucleotides (**Figure 6C**) [27].

#### *7.2.3 Application external forces to eradicate the biofilm*

Both physical and biochemical methods are used to eradicate already formed biofilm. Physical methods entail use of UV radiation whereas biochemical methods use phage lysins, degradative enzymes, metabolites and nitric oxides (**Figure 6D**) [26].

#### **7.3 Treatment methods for biofilm infections**

Biofilm infections can be reduced by using conventional antibiotics, either alone or in combination with additional medicines **(Figure 7).** For example, it was observed that sub-minimum inhibitory concentrations (MICs) of ceftazidime repressed the

#### **Figure 6.**

*Strategies for controlling biofilm infections. (A) Surface treatment. (B) Surface coating. (C) Chemical agents that influence QS. (D) External force [26].*

#### **Figure 7.**

*Schematic illustration of antibiotics-based tactics for preventing the growth of clinically-significant bacterial biofilms [7].*

expression of genes involved in *P. aeruginosa* bacterial adherence and matrix synthesis, decrease biofilm volume, and impede twitching motility [7, 52]. Colistin also greatly decreased *E. coli* biofilms and planktonic cells in a concentration-dependent manner [53]. According to an *in vitro* study, gentamycin released by bone graft replacements can inhibit *E. coli* adhesion at 12 μg/mL and can remove biofilms that have been present for 24 hours at 23 μg/mL [54].

However, because biofilm has emerged, the majority of antibiotics are now given in clinical settings in mixtures with other antibiotics. Despite the fact that vancomycin is still the antibiotic most frequently recommended for *S. aureus* biofilmassociated infections, the rise of vancomycin-resistant *S. aureus* has made it necessary to combine vancomycin with other antibiotics, such as rifampin. Additionally, colistin *Bacterial Biofilm Eradication in Human Infections DOI: http://dx.doi.org/10.5772/intechopen.113341*

and other antibiotics, such tigecycline, have demonstrated synergistic effects *in vitro*, indicating the possibility of their use in clinical settings. Also, it was proven that various strains of *E. coli* linked to UTIs had their biofilm biomass drastically decreased by amikacin, ciprofloxacin, and third-generation cephalosporins. Additionally, it was shown that *Staphylococcal* biofilms developed on titanium devices may be removed within 72 hours with the help of a combined antibiotic therapy of clarithromycin and daptomycin [7].

### **8. Conclusion**

Complex and dynamic interactions between the surface, microorganisms, and EPS are necessary for the development of a biofilm. In addition, biofilms contain a form of bacteria that is common in nature. Their resistance is a major barrier that traditional methods must overcome. However, antimicrobials have not received enough attention at current stage. The spatial heterogeneity in the chemical and microbial composition of biofilms has made it more challenging to execute eradication strategies. For the purpose of preventing infections, this paper highlighted a number of cutting-edge antimicrobials based on nanotechnology and delivery techniques, especially in the context of better penetration and targeted antimicrobial administration inside the biofilm for its eradication.
